Stressed Out Mamas,Their Messed Up Kids
And
How an Enriched Environment Can Fix All That
prenatal [(pree-nayt-l)]
The period between conception and birth.
Last weeks paperLateral Palium in
fishesHippocampus in
mammals
Physiology of Prenatal StressAlters synaptic function (to detriment of
offspring)Gene expression
Decreases synaptic densities in the hippocampus of offspring
Induces marked absence of hippocampal neurogenesis
Reduces density of nitric-oxide producing neurons in dentate and parts of hippocampus in offspring
Prenatal Stressor10 foot shocks
over 30 minutesDaily for 1 week~ 2 weeks before
birth
Enriched Environment (EE)
Enriched EnvironmentEE can reverse cognitive deficits from early life
stressEmotional reactivity, motor skills and spatial
learning Early postnatal EE can counteract deficits in
hippocampal neurogenesis brought on by prenatal stress
Enriched Cage vs. Normal CageEnriched Environment Normal Environment
60 x 50 x 70 cm = 210K cu cm
2 FloorsWood ShavingsRunning wheel, shelter,
toys, chain, swing, tunnels
60 x 40 x 25 cm = 60K cu cm
Bedding?
Questions to be answeredHow does prenatal stress affect synaptic
plasticity in the hippocampusHow does it work after an acute stressor
How does prenatal stress affect a spatial learning task preformed by rats
Can either of these things be reversed by Enriched Environment
Control Offsprin
g
Prenatally Stressed Offspring
Prenatally Stressed Offspring
WITH Environmental
Enrichment
Pregnant Mother
Prenatal Stress?
No Yes
Weaning
Placed in cage with
Enrichment?
No Yes
Prenatal day 19-13
Pregnant mothers
stressed for 7 days.
Birth
Day 0
Postnatal day 22
Prenatally stressed Pups
separated into normal or enriched
environments
Postnatal WEEK 8
Rats killed, hippocampal
slices prepared for
electrophysiology
Control Offsprin
g
Prenatally
Stressed Offsprin
g
Prenatally Stressed Offspring
WITH Environmental
Enrichment
Exp 1. Prenatal Stress and EE
Prenatal day 19-13
Pregnant mothers
stressed for 7 days.
Birth
Day 0
Postnatal day 22
Prenatally stressed Pups
separated into normal or enriched
environments
Postnatal WEEK 8
Rats killed, slices prepared
for electrophysiolo
gy
Exp 2. Prenatal Stress, EE AND acute stressor on offspring
10 foot shocks over 10 minutes before killing
Experiments 1 + 2 electrophysiologyLTP LTDStrengthening of a given
synapseCorrelation to learning
something completely newThe bench is hot
Inhibition of a given synapse
Correlation to learning to disregard something previously learnedThe bench isn’t hot at
night
Recordings were taken from slices in the CA1 region of the hippocampus.
Exp. 1
Exp. 2
Morris Water Maze(Classic Spatial Learning Task)
Morris Water Maze(Classic Spatial Learning Task)6 swimming trials per day/ 4 daysDay 5 platform removed
Measured when rat crossed where platform SHOULD be
ResultsIn a nutshell….
All changes in LTP, LTD and spatial learning brought upon by prenatal stress are reversed with environmental enrichment at an early age.
Effect of prenatal stress on hippocampal neurogenesis + EE reversal
Lemaire, V., Lamarque, S., Moal, M. L., Piazza, P. V., & Abrous, D. N. (2006). Postnatal stimulation of the pups counteracts prenatal stressinduced deficits in hippocampal neurogenesis. Biological Psychiatry, 59, 786–792.
DiscussionPrenatal stress impairs behavior due to
sensitive period of brain circuitry formationLTP depressedLTD enhancedSpatial learning inhibitedAcute stress effects of LTP + LTD exacerbated?
Decrease in hippocampal neurogenesis from prenatal stress
DiscussionMechanisms behind the LTP + LTD?
Prolonged glucocorticoid increaseNorepinephrine increases in hippocampusAcetylcholine increases in hippocampus
Decrease in synaptic gene expressionMost notably NR1 + NR2A
Just because of lack of neurogenesis?NR2B antagonists can reverse the enhanced LTD
effect of prenatal stressNR2B subunit of NMDA receptor thought to play roll
in LTD
DiscussionEnriched Environment is REALLY cool
Reverses most problems associated with prenatal stress in animal models
Use it or loose it?